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Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc

  • Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER (TM) technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures.Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER (TM) technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.show moreshow less

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Author details:Moira Löpfe, Anja Duss, Katerina-Alexandra Zafeiropoulou, Oddny Bjoergvinsdottir, David EglinORCiD, Giuseppino Fortunato, Jürgen Klasen, Stephen J. Ferguson, Karin Würtz-KozakORCiDGND, Olga KrupkovaORCiDGND
DOI:https://doi.org/10.3390/pharmaceutics11090435
ISSN:1999-4923
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/31480533
Title of parent work (English):Pharmaceutics
Publisher:MDPI
Place of publishing:Basel
Publication type:Article
Language:English
Date of first publication:2019/09/01
Publication year:2019
Release date:2020/11/26
Tag:EGCG; degenerative disc disease; drug delivery; electrospraying; inflammation; injectable biomaterial; microparticles
Volume:11
Issue:9
Number of pages:15
Funding institution:IBSA Foundation (2017); Maxi Foundation (CABMM start-up grant 2015)
Organizational units:Humanwissenschaftliche Fakultät / Strukturbereich Kognitionswissenschaften / Department Sport- und Gesundheitswissenschaften
DDC classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Peer review:Referiert
Publishing method:Open Access
Open Access / Gold Open-Access
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